title: Villous trophoblast abnormalities in extremely preterm deliveries with elevated second trimester maternal serum hCG or inhibin-A.
abstract: Elevated levels of the maternal prenatal screening markers hCG and inhibin-A, measured at 15-20 weeks gestation, increase the subsequent risk of severe pre-eclampsia and intra-uterine growth restriction (IUGR). Since both markers are produced by syncytiotrophoblast, we tested the hypothesis that these elevations were due to accelerated differentiation of the villous trophoblast compartment. We performed a retrospective study of 12 cases from our Placenta Clinic with total hCG and/or inhibin-A levels of ≥3.0 multiples of the median that subsequently delivered by 28 weeks gestation and compared their placental pathology findings with 24 gestational age-matched controls. Morphometric analysis demonstrated a 41% reduction in the volume ratio of Ki67 positive cytotrophoblast nuclei to total trophoblast in cases vs controls (Student's T-test; p = 0.028). Distal villous hypoplasia (DVH) was significantly more common in cases (10/12) than controls (4/24); Fisher's exact test, p = 0.002. Wave-like syncytial knot (WLSK) formation was significantly more common in cases (9/12) than controls (1/24); Fisher's exact test, p < 0.0001. WLSK formation was associated with DVH and resulted from accumulation of senescent/apoptotic syncytiotrophoblast nuclei along inherent lines of syncytial nuclear organization. Our data support the hypothesis that elevated second trimester maternal serum levels of total hCG and/or inhibin-A may result from premature accelerated differentiation of the villous cytotrophoblasts. The subsequent pathologic findings in the syncytiotrophoblast could render the pregnancy at risk of severe pre-eclampsia and IUGR.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Fitzgerald
authors.forename: K
authors.initials: K
authors.lastname: Levytska
authors.forename: J
authors.initials: J
authors.lastname: Kingdom
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.forename: D
authors.initials: D
authors.lastname: Baczyk
authors.forename: S
authors.initials: S
authors.lastname: Keating
mesh_terms: D002454:Cell Differentiation; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D005260:Female; D006801:Humans; D007265:Inhibins / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D047928:Premature Birth / Q000473:pathology*; D012189:Retrospective Studies; D014327:Trophoblasts / Q000473:pathology*
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; C422362:inhibin A; D007265:Inhibins